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酒精和高脂饮食诱导的慢性胰腺炎小鼠模型

A Mouse Model of Chronic Pancreatitis Induced by an Alcohol and High Fat Diet.

作者信息

Clinkinbeard T, Kline R H, Zhang L P, McIlwrath S L, Watkins J F, Westlund K N

机构信息

Center for Gerontology, School of Public Health, University of Kentucky, 725 Rose St., Lexington, KY 40536, USA.

Department of Physiology, School of Medicine, University of Kentucky, 800 Rose St., Lexington, KY 40536-0298, USA.

出版信息

Open Pain J. 2017;10(1):81-89. doi: 10.2174/1876386301710010081. Epub 2017 Sep 15.

Abstract

BACKGROUND/AIMS: Study of acute pancreatitis in chemically-induced rodent models has provided useful data; models of alcoholic chronic pancreatitis have not been available in mice. The aim of the present study was to characterize a mouse model of chronic pancreatitis induced solely with an alcohol and high fat (AHF) diet.

METHODS

Mice were fed a liquid high fat diet containing 6% alcohol as well as a high fat supplement (57% total dietary fat) over a period of five months or as control, normal chow . Pain related measures utilized as an index of pain included mechanical sensitivity of the hind paws determined using von Frey filaments and a smooth/rough textured plate. A modified hotplate test contributed information about higher order behavioral responses to visceral hypersensitivity. Mice underwent mechanical and thermal testing both with and without pharmacological treatment with a peripherally restricted μ-opioid receptor agonist, loperamide.

RESULTS

Mice on the AHF diet exhibited mechanical and heat hypersensitivity as well as fibrotic histology indicative of chronic pancreatitis. Low dose, peripherally restricted opiate loperamide attenuated both mechanical and heat hypersensitivity.

CONCLUSION

Mice fed an alcohol and high fat diet develop histology consistent with chronic pancreatitis as well as opioid sensitive mechanical and heat hypersensitivity.

摘要

背景/目的:在化学诱导的啮齿动物模型中对急性胰腺炎的研究已提供了有用的数据;但小鼠中尚无酒精性慢性胰腺炎模型。本研究的目的是对仅用酒精和高脂肪(AHF)饮食诱导的慢性胰腺炎小鼠模型进行特征描述。

方法

给小鼠喂食含6%酒精的液体高脂肪饮食以及高脂肪补充剂(占总膳食脂肪的57%),持续五个月,或作为对照喂食正常食物。用作疼痛指标的与疼痛相关的测量包括使用von Frey细丝和平滑/粗糙纹理板测定后爪的机械敏感性。改良的热板试验提供了有关对内脏超敏反应的高级行为反应的信息。在用外周限制性μ-阿片受体激动剂洛哌丁胺进行药理治疗和不进行药理治疗的情况下,对小鼠进行机械和热测试。

结果

食用AHF饮食的小鼠表现出机械和热超敏反应以及提示慢性胰腺炎的纤维化组织学。低剂量、外周限制性阿片类药物洛哌丁胺可减轻机械和热超敏反应。

结论

喂食酒精和高脂肪饮食的小鼠出现与慢性胰腺炎一致的组织学变化以及对阿片类药物敏感的机械和热超敏反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa69/8317824/7f49560dc941/nihms-1665525-f0001.jpg

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